This invention is concerned with cephalosporin antibiotics. In particular, it concerns cephalosporin antibiotics substituted in the 3'-position with a pyrazinium or substituted pyrazinium group and in the 7-position with a 2-(amino-substituted oxazole, isoxazole or oxadiazole)-2-oximinoacetylamino group.
A number of semi-synthetic cephalosporin antibiotics substituted in the 3-position with a quaternary ammonium group have been described since cephalosporin C.sub.A (pyridine) was prepared by Hale, Newton, and Abraham, Biochem. J. 79, 403 (1961). The well-known clinical antibiotic cephaloridine, 7-(2-thienyl)acetamido-3-pyridinium-1-ylmethyl-3-cephem-4-carboxylate, U.S. Pat. No. 3,449,338, was the second cephalosporin antibiotic to achieve commercial success following the introduction of sodium cephalothin.
Recently, Heymes, et al., U.S. Pat. No. 4,152,432, describe 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-acetoxymethyl-3-ceph em-4-carboxylate as a potent antibiotic. Others have described 3'-quaternary ammonium derivatives of compounds having such an aminothiazole oximino side chain with enhanced potency. For example, O'Callaghan, et al., U.S. Pat. No. 4,258,041, describe the 3-pyridinium-substituted derivative, syn-7-[2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-yl)oxyiminoacetamido]-3- (pyridinium-1-ylmethyl)-3-cephem-4-carboxylate. British patent application No. 2,043,641A describes compounds having like 7-position side chains but substituted in the 3'-position with a pyridazinium group.